This project is designed to define the interactive mechanisms by which changes in hemodynamic variables induce changes in the release of ACTH by the pituitary and in the secretion of cortisol by the adrenal. Attention is directed to the further definition and characterization of the anatomical organization and physiologic control of central neuronal pathways mediating release of ACTH in response to hemodynamic changes. Further attention is directed to the modulation of hymodynamic control of pituitary-adrenal function by the interaction of neural pathways and humoral factors, including the action of steroids, of vasopressin, of angiotensin II and of the endogenous opiates. Special attention is directed to the definition of temporal and quantitative features of the response of ACTH and of cortisol to hemodynamic changes in the presence or absence of nociceptive stimuli, and to the dependence of this response on the time of stimulus presentation and on the past history of stimulation. Parallel studies are proposed to relate to the overall response of the system to central neural processing. Experiments utilize one hemodynamic variable as a stimulus with control of other key hemodynamic variables within narrowly defined limits by means of computer directed closed loop control. Neurophysiological techniques including electrical/chemical stimulation and lesioning, single unit recording, in vivo electrochemical recording of neuro-chemical flux, immunocytochemical localization of hormonally sensitive neural elements and anatomical tracing of neural pathways are applied in conjunction with RIA measurements of ACTH, cortisol, and Beta-endorphin and with HPLC measurements of adrenal cortical and medullary hormones. These proposed studies are directed at the examination of central and peripheral mechanisms mediating the pituitary and adrenal responses to a controlled physiologic stimulus, such as hemorrhage, and the results will attempt to elucidate the complex interactions of neuronal and hormonal factors in order to provide a comprehensive description of the function of this neuroendocrine system.